Mussel adhesive proteins (MAPs) are remarkable underwater adhesive polymers that form tenacious bonds to anchor marine organisms onto the substrates upon which they reside. Even in the presence of water, the adhesive protein plaques form extremely tenacious bonds to solid objects, an accomplishment which is not often matched by synthetic adhesives. These protein 'glues' can be characterized as having a high concentration of L- 3,4-dihydroxyphenylalanine (DOPA), an amino acid that is believed to be responsible for both adhesive and crosslinking characteristics of MAPs. However, the chemical reactions in which DOPA residues can participate are complex and not fully understood, particularly as they relate to adhesion and crosslinking. Although simple bulk shear adhesion tests have yielded important practical evidence that DOPA-mimetic polymers may be useful as adhesives, the design of the polymers and the techniques that were previously used for measuring adhesion are not ideal for elucidating the underlying molecular aspects of bioadhesion. Thus, new strategies for adhesion testing and the development of the next generation of DOPA-containing polymers are needed, in particular those that enable detailed examination of DOPA chemical interactions and their contribution to adhesion. The goals of this research are to employ molecular-level adhesion experiments to gain a detailed understanding of the role of DOPA in biological adhesion, and to use this information to motivate the design of new DOPA-containing macromolecular biomaterials. New DOPA-mimetic polymers will be synthesized and adhesive properties assessed by a versatile fracture mechanics based adhesion test. In-situ control of DOPA chemical reactions will be used to reveal fundamental relationships between adhesive performance and DOPA content, DOPA oxidation, peptide composition, and substrate chemistry. Finally, an in vitro cytotoxicity assay will be used to assess the biological response to the DOPA-mimetic polymers. At the conclusion of this study we will have gained considerable insight into the fundamental role of DOPA and oxidized forms of DOPA on adhesion in biological systems, and utilized this knowledge for the rational design of new adhesive biomaterials.